Holistic engineering of cell-free systems through proteome-reprogramming synthetic circuits
| Autor: | Yao Liu, Conary Meyer, Marjorie L. Longo, Cheemeng Tan, Luis E. Contreras-Llano, Sierin Lim, Mridul Sarker |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
Proteome Computer science Systems biology 1.1 Normal biological development and functioning Science Gene regulatory network General Physics and Astronomy Bioengineering Computational biology 01 natural sciences General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Synthetic biology Bacterial Proteins 010608 biotechnology Genetics Escherichia coli Gene Regulatory Networks lcsh:Science 030304 developmental biology Electronic circuit 0303 health sciences Multidisciplinary Cell-Free System Cas9 fungi Biological techniques General Chemistry Crosstalk (biology) Metabolic Engineering Protein Biosynthesis lcsh:Q Synthetic Biology Generic health relevance Reprogramming Metabolic Networks and Pathways Biotechnology |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-10 (2020) Nature communications, vol 11, iss 1 |
| ISSN: | 2041-1723 |
| Popis: | Synthetic biology has focused on engineering genetic modules that operate orthogonally from the host cells. A synthetic biological module, however, can be designed to reprogram the host proteome, which in turn enhances the function of the synthetic module. Here, we apply this holistic synthetic biology concept to the engineering of cell-free systems by exploiting the crosstalk between metabolic networks in cells, leading to a protein environment more favorable for protein synthesis. Specifically, we show that local modules expressing translation machinery can reprogram the bacterial proteome, changing the expression levels of more than 700 proteins. The resultant feedback generates a cell-free system that can synthesize fluorescent reporters, protein nanocages, and the gene-editing nuclease Cas9, with up to 5-fold higher expression level than classical cell-free systems. Our work demonstrates a holistic approach that integrates synthetic and systems biology concepts to achieve outcomes not possible by only local, orthogonal circuits. Synthetic biological modules can be used to reprogram host proteomes, which in turn enhance the function of the synthetic modules. The authors use this holistic synthetic biology approach to engineer a more favorable environment for cell-free protein synthesis. |
| Databáze: | OpenAIRE |
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